We have extensively evaluated the neutralizing activity of our most promising anti-HIV antibodies m9 and X5 in different antibody formats, scFv, Fab and IgG1. The crystal structure of Fab X5 in complex with gp120-CD4 was determined in collaboration with P. Kwong. It provides molecular details of how Fab X5 interacts with HIV-1 and could help in the design of novel inhibitors. The success with the identification and characterization of X5, and the transition of our Laboratory to a Nanobiology Program shifted the focus of my group research efforts to the identification and characterization of novel potent antibodies against viruses and cancer that can be also used to bestow binding specificities to nanoparticles with implications for development of novel diagnostics, prophylactics, therapeutics and vaccines. My interest in nanotechnology originated more than 36 years ago when I began my scientific research on thin liquid films in colloid systems that possess different properties from those of the same material in bulk when their size becomes smaller than 100-1000 nm and is now renewed with a major goal to develop nanobiology-based cancer therapeutics.We have identified a number of novel antibodies to gp120 and to gp41 as well as to cancer-related antigens including IGF-II. Responding to the threat of bioterrorism and to the health crisis caused by the SARS coronavirus (SCV), we identified and characterized neutralizing antibodies to the biodefense-related Hendra virus (HeV) and Nipah virus (NiV), and to the SCV. We also solved the structure of SCV receptor-binding domain complex with our potent antibody m396. I have also been involved in other studies in collaboration with intramural and extramural groups that resulted in important findings. The identification of ephrinB2 as a functional receptor for HeV and NiV is an interesting example of how our virus-related research could have unanticipated implications for cancer. EphrinB2 and its receptors, EphB2 and EphB4, have recently been recognized as important cancer-related proteins; we are currently developing antibodies targeting ephrinB2 that could be used against cancer, HeV and NiV. We plan to continue to identify novel potent nhmAbs against cancer, HIV-1, and biodefense-related viruses, elucidate mechanisms of their interactions with antigens and with nanoparticles, and develop antibodies and antibody-guided nanoparticles for diagnosis, prevention and treatment of diseases, and as research reagents. The most promising of these will be evaluated in animal models and hopefully in human clinical trials.